3-127695038-T-C

Variant names:

• chr3-127695038-T-C
• rs4881
• NM_007283.7:c.753A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_007283.7(MGLL):​c.753A>G​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 1,613,990 control chromosomes in the GnomAD database, including 7,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (950 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6903 hom.)
• Consequence: MGLL NM_007283.7 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0500
• Publications: 20 publications found

Genes affected

MGLL (HGNC:17038): (monoglyceride lipase) This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.07).
• BP6: Variant 3-127695038-T-C is Benign according to our data. Variant chr3-127695038-T-C is described in ClinVar as Benign. ClinVar VariationId is 3056921.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007283.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	NM_007283.7	MANE Select	c.753A>G	p.Leu251Leu	synonymous	Exon 7 of 8	NP_009214.1
	MGLL	NM_001388312.1		c.831A>G	p.Leu277Leu	synonymous	Exon 8 of 9	NP_001375241.1
	MGLL	NM_001388313.1		c.801A>G	p.Leu267Leu	synonymous	Exon 8 of 9	NP_001375242.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.753A>G	p.Leu251Leu	synonymous	Exon 7 of 8	ENSP00000265052.5
	MGLL	ENST00000398101.7	TSL:1	n.1144A>G		non_coding_transcript_exon	Exon 5 of 6
	MGLL	ENST00000476682.1	TSL:1	n.3724A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16194 AN: 152082 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.00907

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0989

GnomAD2 exomes AF: 0.0839 AC: 20936 AN: 249476 AF XY: 0.0851

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0516

Gnomad ASJ exome AF: 0.0821

Gnomad EAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0609

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.0901

GnomAD4 exome AF: 0.0935 AC: 136682 AN: 1461790 Hom.: 6903 Cov.: 32 AF XY: 0.0933 AC XY: 67847 AN XY: 727200

African (AFR) AF: 0.162 AC: 5412 AN: 33478

American (AMR) AF: 0.0559 AC: 2502 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 2117 AN: 26132

East Asian (EAS) AF: 0.00680 AC: 270 AN: 39700

South Asian (SAS) AF: 0.0779 AC: 6722 AN: 86254

European-Finnish (FIN) AF: 0.0644 AC: 3439 AN: 53374

Middle Eastern (MID) AF: 0.0683 AC: 394 AN: 5768

European-Non Finnish (NFE) AF: 0.0992 AC: 110319 AN: 1111970

Other (OTH) AF: 0.0912 AC: 5507 AN: 60392

GnomAD4 genome AF: 0.106 AC: 16198 AN: 152200 Hom.: 950 Cov.: 32 AF XY: 0.102 AC XY: 7575 AN XY: 74428

African (AFR) AF: 0.160 AC: 6652 AN: 41528

American (AMR) AF: 0.0859 AC: 1312 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3468

East Asian (EAS) AF: 0.00909 AC: 47 AN: 5168

South Asian (SAS) AF: 0.0768 AC: 371 AN: 4830

European-Finnish (FIN) AF: 0.0582 AC: 617 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0981 AC: 6667 AN: 67994

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.0965 Hom.: 1218

Bravo AF: 0.111

Asia WGS AF: 0.0570 AC: 200 AN: 3478

EpiCase AF: 0.0963

EpiControl AF: 0.106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MGLL-related disorder Benign:1

Jan 02, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.6
DANN	Benign	0.69
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4881; hg19: chr3-127413881; COSMIC: COSV54024486;